((1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-[(1S,2S)-2-(1-trityl-1H-imidazol-4-yl)-cyclopropyl]-methanone | 201669-69-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: ((1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-[(1S,2S)-2-(1-trityl-1H-imidazol-4-yl)-cyclopropyl]-methanone
• 英文别名: [(1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3lambda6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]-[(1S,2S)-2-(1-tritylimidazol-4-yl)cyclopropyl]methanone；[(1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3λ6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]-[(1S,2S)-2-(1-tritylimidazol-4-yl)cyclopropyl]methanone
• CAS: 201669-69-4
• 化学式: C₃₆H₃₇N₃O₃S
• 分子量: 591.774
• InChiKey: USUAXIYUQGKVCY-MGXGTVKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  43
• 可旋转键数：
  6
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  80.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-[(1S,2S)-2-(1-trityl-1H-imidazol-4-yl)-cyclopropyl]-methanone 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以90%的产率得到(1S,2S)-1-(1-三苯基甲基-1H-咪唑-4-基)环丙烷-2-羧酸
  参考文献：
  名称：

  Diastereoselective synthesis of trans-2-(1-triphenylmethyl-1H-imidazol-4-yl)cyclopropanecarboxylic acids: key intermediates for the preparation of potent and chiral histamine H3 receptor agents

  摘要：

  Procedures for the preparation of both enantiomers of trans-2-(1-triphenylmethyl-1H-imidazol-4-yl)-cyclopropanecarboxylic acid are described. The key step in the synthesis is a 3:1 diastereoselective cyclopropanation of (5R)-trans-4-aza-10,10-dimethyl-3-thia-4-(3-(1-triphenylmethyl-1H-imidazol-4-yl)prop-2-enoyl)tricyclo[5.2.1.0<1,5>]decane-3,3-dione using trimethylsulfoxonium ylide. These cyclopropanes are useful for the preparation of H-3 receptor agents. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10137-8
• 作为产物：
  描述：

  (2R)-bornane-10,2-sultam 在 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 氯仿 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 ((1S,5R,7R)-10,10-dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-[(1S,2S)-2-(1-trityl-1H-imidazol-4-yl)-cyclopropyl]-methanone
  参考文献：
  名称：

  Diastereoselective synthesis of trans-2-(1-triphenylmethyl-1H-imidazol-4-yl)cyclopropanecarboxylic acids: key intermediates for the preparation of potent and chiral histamine H3 receptor agents

  摘要：

  Procedures for the preparation of both enantiomers of trans-2-(1-triphenylmethyl-1H-imidazol-4-yl)-cyclopropanecarboxylic acid are described. The key step in the synthesis is a 3:1 diastereoselective cyclopropanation of (5R)-trans-4-aza-10,10-dimethyl-3-thia-4-(3-(1-triphenylmethyl-1H-imidazol-4-yl)prop-2-enoyl)tricyclo[5.2.1.0<1,5>]decane-3,3-dione using trimethylsulfoxonium ylide. These cyclopropanes are useful for the preparation of H-3 receptor agents. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10137-8

文献信息

• An Efficient Multigram Synthesis of the Potent Histamine H₃ Antagonist GT-2331 and the Reassessment of the Absolute Configuration
  作者：Huaqing Liu、Francis A. Kerdesky、Lawrence A. Black、Michael Fitzgerald、Rodger Henry、Timothy A. Esbenshade、Arthur A. Hancock、Youssef L. Bennani

  DOI：10.1021/jo035264t

  日期：2004.1.1

  GT-2331 is a potent histamine H3 antagonist which has entered clinical trials. Efficient multigram syntheses of this compound and its enantiomer are described. The literature reports that GT-2331 is the dextrorotatory (+), more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole with the absolute configuration of (1R,2R)-1. However, we found that the dextrorotatory, more potent

  GT-2331是一种有效的组胺H 3拮抗剂，已进入临床试验。描述了该化合物及其对映异构体的有效数克合成。文献报道GT-2331是4- [2-（5,5-二甲基己基-1-炔基）环丙基] -1 H-咪唑的右旋（+），更有效的对映异构体，其绝对构型为（1 R，2 R）-1。然而，我们发现4- [2-（5,5-二甲基己基-1-炔基）环丙基] -1 H-咪唑的右旋，更有效的对映异构体具有（1 S，2 S）绝对构型。我们建议重新考虑GT-2331的绝对配置。